17β-Estradiol Inhibites Tumor Necrosis Factor-α Induced Apoptosis of Human Nucleus Pulposus Cells via the PI3K/Akt Pathway

Wang, Tao; Yang, Sidong; Liu, Sen; Wang, Hui; Liu, Huan; Ding, Wenyuan

doi:10.12659/msm.900310

Cited by 26 publications

(17 citation statements)

References 49 publications

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“…The present study investigated the effect of 17β-E2 on human NP cells; however, the findings of the present study are limited. The results of the present study were used as preliminary data for our subsequent study, which demonstrated that 17β-E2 inhibits TNF-α-induced apoptosis in human NP cells via the PI3K/Akt pathway ( 46 ). Further signaling mechanisms underlying the anti-apoptotic effects of 17β-E2 in human NP cells will require further investigation.…”

Section: Discussionmentioning

confidence: 88%

Protective role of 17β-estradiol on tumor necrosis factor-α-induced apoptosis in human nucleus pulposus cells

Liu

Yang

et al. 2017

Molecular Medicine Reports

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The molecular mechanisms underlying protection and pathogenesis in spinal degenerative diseases remain unclear. Tumor necrosis factor-α (TNF-α) has been demonstrated to induce apoptosis of intervertebral disc (IVD) cells during IVD degeneration, and 17β-estradiol (17β-E2) has a protective effect against IVD cell apoptosis. However, the underlying molecular mechanism by which 17β-E2 protects nucleus pulposus (NP) cells remains to be investigated. The aim of the present study was to evaluate whether 17β-E2 modulates apoptosis of human NP cells induced by TNF-α. In addition, the concentration-response effect of 17β-E2 on human NP cells was investigated. Human NP cells were cultured in complete medium, which was replaced every three days until the culture was ~80% confluent. Cells were treated with 100 ng/ml TNF-α for 48 h, with or without pretreatment with various concentrations of 17β-E2, and ICI 182,780, for 30 min. Morphologic alterations characteristic of apoptosis were observed by inverted phase-contrast microscopy and Hoechst 33258 staining; the apoptosis rate was analyzed by flow cytometry. A Cell Counting kit-8 assay was used to assess cell proliferation. Furthermore, caspase-3 activity was determined and proteins associated with apoptosis were analyzed by western blotting. The level of apoptosis and caspase-3 activity in human NP cells increased, whereas proliferation and the expression of poly ADP-ribose polymerase decreased following TNF-α treatment. These effects of TNF-α were abolished by pretreatment with 17β-E2 in a concentration-dependent manner. The results of the present study indicated that 17β-E2 serves a critical role in the survival of degenerative human NP cells.

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Section: Discussionmentioning

confidence: 88%

Protective role of 17β-estradiol on tumor necrosis factor-α-induced apoptosis in human nucleus pulposus cells

Liu

Yang

et al. 2017

Molecular Medicine Reports

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“…Previous studies indicated that activation of PI3K/AKT signaling attenuated NP cells apoptosis induced by high-magnitude compression [23] or hyperosmotic conditions [24]. In addition, PI3K/AKT could protect NP cells against apoptosis induced by some cytokines, such as IL-1β [25] and TNF-ɑ [26]. Thus, we supposed that whether PI3K/Akt also played a protective effect on hNP-MSCs under hypoxia and nutrition deficiency.…”

Section: Introductionmentioning

confidence: 84%

The protective effects of PI3K/Akt pathway on human nucleus pulposus mesenchymal stem cells against hypoxia and nutrition deficiency

Tian

Chen

et al. 2020

J Orthop Surg Res

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Background: To study the effects of hypoxia and nutrition deficiency mimicking degenerated intervertebral disc on the biological behavior of human nucleus-derived pulposus mesenchymal stem cells (hNP-MSCs) and the role of PI3K/Akt pathway in the process in vitro. Methods: hP-MSCs were isolated from lumbar disc and were further identified by their immunophenotypes and multilineage differentiation. Then, cells were divided into the control group, hypoxia and nutrition deficiency group, the LY294002 group, and insulin-like growth factor 1 (IGF-1) group. Then cell apoptosis, the cell viability, the caspase 3 activity, and the expression of PI3K, Akt, and functional genes (aggrecan, collagen I, and collagen II) were evaluated. Result: Our work showed that isolated cells met the criteria of International Society for cellular Therapy. Therefore, cells obtained from degenerated nucleus pulposus were definitely hNP-MSCs. Our results showed that hypoxia and nutrition deficiency could significantly increase cell apoptosis, the caspase 3 activity, and inhibit cell viability. Gene expression results demonstrated that hypoxia and nutrition deficiency could increase the relative expression of PI3K and Akt gene and inhibit the expression of functional genes. However, when the PI3K/Akt pathway was inhibited by LY294002, the cell apoptosis and caspase 3 activity significantly increased while the cell viability was obviously inhibited. Quantitative real-time PCR results showed that the expression of functional genes was more significantly inhibited. Our study further verified that the abovementioned biological activities of hNP-MSCs could be significantly improved by IGF1. Conclusions: PI3K/Akt signal pathway may have protective effects on human nucleus pulposus-derived mesenchymal stem cells against hypoxia and nutrition deficiency.

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“…However, the overall survival rate for patients with osteosarcoma has not markedly improved since the introduction of neoadjuvant chemotherapy, radiotherapy and surgery ( 42 ). It has been suggested that the PI3K/AKT signaling pathway serves an essential role in human carcinoma cells as it regulates cell growth, proliferation and apoptosis ( 43 , 44 ). In the present study, it was revealed that lnPTENP1 regulates the growth of osteosarcoma cells via the PI3K/AKT signaling pathway.…”

Section: Discussionmentioning

confidence: 99%

Long non‑coding RNA phosphatase and tensin homolog pseudogene 1 suppresses osteosarcoma cell growth via the phosphoinositide 3‑kinase/protein kinase B signaling pathway

et al. 2018

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Osteosarcoma is a common type of human carcinoma, which exhibits a high metastasis and recurrence rate. Previous studies have indicated that long non-coding RNA phosphatase and tensin homolog pseudogene 1 (lnPTENP1) has tumor suppressive action by modulating PTEN expression in different types of tumor cells. However, the potential mechanism by which lnPTENP1 has an effect in osteosarcoma cells remains elusive. In the present study, the role of lnPTENP1 in osteosarcoma cells was investigated and the possible mechanisms by which it functions were explored. It was revealed that lnPTENP1 transfection significantly inhibited osteosarcoma cell growth, proliferation, migration and invasion. LnPTENP1 transfection also significantly promoted apoptosis in Mg63 cells treated with tunicamycin. Further analysis revealed that lnPTENP1 transfection regulated osteosarcoma cell growth via the PI3K/AKT signaling pathway. In vivo assays revealed that lnPTENP1 transfection significantly inhibited osteosarcoma tumor growth and significantly increased the protein expression and phosphorylation levels of PI3K and AKT. In conclusion, the results of the present study indicated that lnPTENP1 may inhibit osteosarcoma cell growth via the PI3K/AKT signaling pathway, which may be a potential novel target for human osteosarcoma therapy.

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17β-Estradiol Inhibites Tumor Necrosis Factor-α Induced Apoptosis of Human Nucleus Pulposus Cells via the PI3K/Akt Pathway

Cited by 26 publications

References 49 publications

Protective role of 17β-estradiol on tumor necrosis factor-α-induced apoptosis in human nucleus pulposus cells

Protective role of 17β-estradiol on tumor necrosis factor-α-induced apoptosis in human nucleus pulposus cells

The protective effects of PI3K/Akt pathway on human nucleus pulposus mesenchymal stem cells against hypoxia and nutrition deficiency

Long non‑coding RNA phosphatase and tensin homolog pseudogene 1 suppresses osteosarcoma cell growth via the phosphoinositide 3‑kinase/protein kinase B signaling pathway

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